青藤碱N-四氮唑和N-噁二唑杂环衍生物的设计与合成

Design and Synthesis of N-Tetrazole and N-Oxadiazole Heterocyclic Derivatives of Sinomenine

建立了两个新的合成路线,在青藤碱D环的N原子上构建了N-四氮唑和N-1,3,4-噁二唑取代的杂环衍生物,共获得了34个新的青藤碱杂环衍生物.以青藤碱为原料,通过溴化氰取代生成N-CN青藤碱,再与叠氮化钠通过1,3-偶极环加成反应,生成了N-四氮唑青藤碱.苄氯类试剂与四氮唑发生取代反应生成青藤碱N-四氮唑杂环衍生物;酰氯类试剂与四氮唑通过酰化反应和惠思根重排反应生成青藤碱N-1,3,4-噁二唑杂环衍生物.方法简单,条件温和,产率优良.此工作为天然产物结构修饰提供了新的方法,扩大了青藤碱衍生物库,为潜在的青藤碱药物活性研究提供了药物分子设计方法.

Two new synthesis methods were established,N-tetrazole and N-1,3,4-oxadiazole substituted heterocyclic derivatives of sinomenine were constructed on the N atom of D-ring,and 34 new sinomenine heterocyclic derivatives were synthesized.N-CN sinomenine at 17-position was generated by substituted reaction between cyanogen bromide and sinomenine,and then N-tetrazole sinomenine was achieved by 1,3-dipolar cycloaddition reaction with NaN3.The reaction of tetrazole with benzyl chloride produced N-tetrazole heterocyclic derivatives of sinomenine.N-1,3,4-Oxadiazole heterocyclic derivatives of sinomenine were obtained by acylation reaction and the Huisigen rearrangement reaction of tetrazole with acyl chloride reagents.These methods with mild condition gave good to excellent yields.This method provides new methods for structural modification of natural products,the synthesized compounds expand the library of sinomenine derivatives,and this work provides a basis study for drug molecular design and potential activity study.